The present study aimed to use the syringe exchange setting in order to facilitate transfer or heroin users into evidence-based substitution treatment with methadone or buprenorphinenaloxone. Out-of-treatment heroin-dependent patients were recruited from a syringe exchange program and actively referred to a research substitution treatment facility. Among 75 patients who were included and underwent baseline evaluation, 71 were successfully referred and started treatment. Segmental hair analysis was used to investigate previous drug abuse, abstinence from drugs of abuse during treatment as well as to confirm compliance to substitution treatment. Hair samples were taken at admission and then after approximately 3 months of treatment.

Hair samples were segmented into 5 segments (5, 5, 5, 10, 10mm) and subjected to qualitative UHPLC-TOF screening for 30 drugs of abuse to elucidate previous drug use patterns. Hair samples were also segmented into 5 segments, washed and quantitation of mu-agonists and sedatives were performed using LC-MSMS including the substitution medications methadone and buprenorphine.

Base line results from the UHPLC-TOF screening indicated an extensive poly-drug abuse of different opioids including heroin (74%), methadone (79%), fentanyl (16%), buprenorphine (16%) and tramadol (26%) as well as use of stimulants such as amphetamine (32%) together with sedatives (74%) of both the common benzodiazepine group and zopiclone and zolpidem. The segmental analysis showed even or decreasing concentrations of 6-acetylmorphine in the hair confirming continuous use of heroin but suggesting infrequent use or lower doses prior to inclusion. After the initiation of treatment the use of illicit opioids decreased dramatically and most subjects abstained from heroin when given methadone or buprenorphine. 50% had no positive segment during the treatment period and 15% were only positive in one or two of the distal segments which could be interpreted as remnants from dormant hair. However, the use of benzodiazepines and other sedatives (80%) was very common during treatment with alprazolam and clonazepam as the most frequent encounters.

The mean methadone dose was 85mg/d (N=12) and the mean concentrations of EDDP and methadone were 0.46ng/mg and 8.8ng/mg, respectively. The concentrations of methadone in hair did not correlate to the dose between subjects but there were clear relationships within patients when doses were escalated during titration. Three patients continued to use heroin and two continued their use of amphetamine. In two of these subjects the methadone concentrations from decreased to half the initial concentrations suggesting that the prescribed dose was diverted rather than taken. Buprenorphine was only detected in 1 patient and norbuprenorphine in 3 patients even though doses between 8 and 24mg/d was given (N=7).

We conclude that segmental hair analysis was a good clinical tool to assess drug use histories prior to inclusion into substitution treatment and to prove abstinence from other drugs during treatment. The dose concentration relationship was weak but may be used within a patient to investigate dose changes or non-compliance for methadone. We believe that data from living subjects entering treatment may provide a basis for interpretation of acute heroin overdoses where abstinence have been suggested as a major factor contributing to death.